Towards the identification of a mesoscale neural systems logic underlying innate behaviors

识别先天行为背后的中尺度神经系统逻辑

基本信息

批准号：
10734660
负责人：
Stefanos Stagkourakis
金额：
$ 12.21万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10734660
关键词：
Address Affect Aggressive behavior Amygdaloid structure Anatomy Animals Anterior Area Award Behavior Behavior Control Behavioral Behavioral Paradigm Brain Brain imaging Brain region Cell Nucleus Chronic Cognition Communication Complement Computer software Custom Data Development Discipline Electrophysiology (science)Emotional Exhibits FOS gene Female Financial Hardship Fluoxetine Fright Goals Grain Human Hypothalamic structure Image Instinct Investigation Laboratory mice Learning Logic Maps Measurement Medical Mental disorders Mentors Methodology Methods Molecular Monitor Mus Neurons Neurosciences Partner in relationship Pattern Phase Physiological Population Prefrontal Cortex Prevalence Reagent Research Resolution Risperidone Role Sex Offenses Shapes Silicon Social isolation Societies Spatial Distribution System Technology Testing Therapeutic Training Vision Work activity marker analysis pipeline behavior influence behavior prediction behavioral plasticity cell type cognitive process conditioned fear design experience experimental study extracellular family burden frontier generalized anxiety in vivo insight interest machine learning method male neural new technology novel novel therapeutics pharmacologic predictive modeling programs response segregation skills social theories therapeutically effective tool

项目摘要

Project Summary/Abstract Innate behaviors, also known as instincts, are essential for the survival of all species in the animal kingdom, including humans. Of great interest is understanding how the experience-induced behavioral plasticity observed in innate behaviors can lead to maladaptive behavioral expressions, including uncontrolled aggression, sex offenses, and generalized anxiety. Such mental disorders carry a substantial emotional and financial burden to families and society, rendering the development of effective therapeutic approaches of high significance. The neural substrates of innate behaviors are distributed across numerous brain regions. An essential step towards understanding how the brain orchestrates behavior is to identify how inter-region interactions of neural activity influence behavior in freely moving animals. However, methodological limitations have largely restricted such investigations to single nuclei, while the deep brain remains to date inaccessible to in vivo mesoscale neural recordings in freely moving animals. The research proposed here uses custom-designed technology to break this methodological barrier, making possible recordings with single-unit resolution across twenty subregions of the deep brain (hypothalamus) in freely moving, innate behavior-expressing mice. In Aim 1, using this technology, I will investigate the presence of behavior-specific mesoscale hypothalamic neural features in the innate and learned expressions of social and fear-related behaviors. I will test whether the activity of specific brain regions can predict specific behaviors, and I will identify the spatial distribution of hypothalamic clusters exhibiting behavior-tuning or mixed selectivity. In Aim 2, I will dissect how aggression- or fear-conditioning alters mesoscale neural activity dynamics and test the effect of chronic administration of pharmacological reagents known to reduce the expression of maladaptive social and fear behaviors. Lastly, in Aim 3 – the independent phase of the award, I will expand the use of these tools to investigate mesoscale neural activity dynamics across diverse areas of the corticolimbic system, seeking to identify local and global principles that guide the expression of the physiological and maladaptive forms of innate behaviors. Collectively, the above approaches target the development of an experimental and analytical platform to address fundamental questions of systems neuroscience on the mesoscale mechanisms that govern the expression of innate behaviors. Following these initial steps, this work will be complemented by experimentation aiming to test whether the identified neural features in the behaviors of interest have a causal role. Through the mentored phase of this award, my vision is to build a highly complementary skillset to the one I acquired during my graduate training, and create a unique, state-of-the-art independent research program. By pursuing work spanning diverse disciplines, including molecular, cellular, systems neuroscience, behavioral and computational approaches, I am committed to developing a mechanistic understanding of the neural basis of innate behaviors, with the potential to lead to advanced therapeutic solutions.

项目概要/摘要先天行为，也称为本能，对于动物王国中所有物种的生存至关重要，包括人类在内，人们非常感兴趣的是了解如何观察到经验引起的行为可塑性。先天行为可能导致适应不良的行为表达，包括不受控制的攻击性、性行为犯罪和广泛性焦虑会给人带来沉重的情感和经济负担。家庭和社会，开发有效的治疗方法具有重要意义。先天行为的神经基础分布在许多大脑区域中，这是一个重要的步骤。了解大脑如何协调行为就是确定神经区域间的相互作用如何活动影响自由活动动物的行为然而，方法学的局限性在很大程度上受到限制。这种针对单核的研究，而深部大脑迄今为止仍然无法进入体内中尺度神经这里提出的研究使用定制设计的技术来打破记录。这种方法上的障碍，使得跨二十个次区域以单一单位分辨率进行记录成为可能自由活动、表达先天行为的小鼠的深部大脑（下丘脑）。在目标 1 中，我将使用该技术研究行为特异性中尺度下丘脑的存在我将测试社交和恐惧相关行为的先天和后天表达的神经特征。特定大脑区域的活动可以预测特定行为，我将识别特定大脑区域的空间分布在目标 2 中，我将剖析表现出行为调节或混合选择性的下丘脑簇。恐惧调节改变中尺度神经活动动力学并测试长期施用的效果已知可减少不良社交和恐惧行为表现的药理学试剂。目标 3 – 奖项的独立阶段，我将扩大这些工具的使用范围来研究中尺度神经网络皮质边缘系统不同区域的活动动态，寻求确定局部和全局原则它指导先天行为的生理和适应不良形式的表达。总的来说，上述方法的目标是开发一个实验和分析平台解决系统神经科学关于控制神经系统的中尺度机制的基本问题在这些初始步骤之后，这项工作将通过实验得到补充。旨在测试所识别的感兴趣行为中的神经特征是否具有因果作用。通过该奖项的指导阶段，我的愿景是建立一套与我的技能高度互补的技能在我的研究生培训期间获得的知识，并创建了一个独特的、最先进的独立研究项目。追求跨学科的工作，包括分子、细胞、系统神经科学、行为和计算方法，我致力于发展对神经基础的机械理解天生的行为，有可能带来先进的治疗解决方案。